Rhinologically active substances

ABSTRACT

Acyclic ethers can be used as rhinologically active substances. In the regions of the mouth, the throat and the airways they produce a refreshing and clearing feeling.

FIELD OF THE INVENTION

[0001] The invention relates to rhinologically active substances whichgive rise to a refreshing and clearing feeling in the area of the mouth,the throat and the airways, and to preparations which comprise thesecompounds.

BACKGROUND OF THE INVENTION

[0002] 1,8-Cineole (eucalyptol) is a substance which is used in largeamounts as a rhinologically active substance in pharmaceuticalpreparations, oral care preparations, such as toothpastes andmouthwashes, and confectionery products, such as cough sweets andchewing-gum, especially because of its property of producing acooling-refreshing and thus clearing feeling in the region of the mouth,the throat and the airways. In addition to this effect, 1,8-cineole(eucalyptol), however, has a strong typical flavor, which, because ofits pronounced medicinal note, is perceived as unpleasant by manyconsumers.

[0003] There is, therefore, a requirement for substances which, in asimilar manner to 1,8-cineole (eucalyptol), produce a cooling-refreshingand thus, clearing feeling as a rhinologically active compound in theregion of the mouth, the throat and the airways, especially in the nasalcavity, and in the pharyngeal cavity, but which do not have such astrong and unpleasant typical taste.

[0004] The advantage of such rhinologically active substances is thatthey are universally usable, that is to say can be used in preparationshaving a multiplicity of aromas of the most varying flavor notes.

[0005] Lower alkyl ethers of isobornane, here particularly of methylisobornyl ether (Food Chem. Toxicol. 30 (Suppl.), 53S (1992), and ofbomane, for example bornyl methyl ether and bornyl ethyl ether, (U.S.Pat. No. 4,131,687) have already been known for a relatively long timeas fragrance and aroma substances having fresh, herb-like, rosemary-likeor eucalyptus-like sensory properties. However, because of their strongtypical flavor, they cannot be used as replacement products for1,8-cineole (eucalyptol) in the sense described above.

SUMMARY OF THE INVENTION

[0006] New rhinologically active substances have been found, which areof the formula

[0007] wherein

[0008] x is 0 or 1,

[0009] R¹ denotes an alkyl group having 1 to 4 carbon atoms,

[0010] R² denotes a methyl or ethyl group and

[0011] R³ denotes a monocyclic carbon system having 5, 6, 7 or 8 carbonatoms that can be unsubstituted or substituted with further alkyl groupshaving 1 to 4 carbon atoms or alkenyl groups having 2 to 4 carbon atoms.

DETAILED DESCRIPTION OF THE INVENTION

[0012] The inventive new rhinologically active substances are acyclicethers.

[0013] The alkyl group having 1 to 4 carbon atoms can be methyl, ethyl,propyl, isopropyl, butyl or isobutyl.

[0014] The alkenyl group having 2 to 4 carbon atoms can be vinyl,2-propenyl, allyl or 2-buten-1-yl.

[0015] The radical R³ can be unsubstituted or can be substituted, forexample, with 1 to 3 methyl groups or with 1 isopropyl group or with 1methyl group and 1 isopropyl group or with 1 methyl group and 1,2-propenyl group.

[0016] The inventive rhinologically active substances exhibit anactivity comparable to 1,8-cineole (eucalyptol) with respect to arefreshing clearing feeling in the mouth, pharyngeal cavity and theairways, without producing an unpleasant taste sensation.

[0017] These rhinologically active substances, in addition to theiractivity of producing a refreshing clearing feeling in the mouth,pharyngeal cavity and the airways, exhibit fresh, ethereal, minty,cooling, sweet and fruity flavor notes and are therefore, alsooutstandingly suitable as flavor compounds.

[0018] The fact that the inventive rhinologically active compoundsexhibit an activity comparable to 1,8-cineole (eucalyptol), with respectto a refreshing clearing feeling in the mouth, pharyngeal cavity and theairways, was surprising and not predictable to the extent that theinventive ethers do not have a cyclic structure like 1,8-cineole(eucalyptol), but have an acyclic structure.

[0019] Preferred rhinologically active compounds in the context of thepresent invention are compounds of the formula

[0020] wherein

[0021] x can have the value 0 or 1,

[0022] R¹ denotes a methyl or ethyl group,

[0023] R² denotes a methyl or ethyl group and

[0024] R³ denotes a monocyclic carbon system having 6 or 7 carbon atomsthat can be unsubstituted or substituted with further alkyl groupshaving 1 to 3 carbon atoms and/or alkenyl groups having 3 carbon atoms.

[0025] The present flavor compounds, render pleasantly tasting flavorcompounds, which have the activity of causing a refreshing clearingfeeling in the mouth, pharyngeal cavity and the airways. The inventiverhinologically active compounds are selected from the group of l-menthylmethyl ether, d-menthyl methyl ether, dl-menthyl methyl ether, menthylethyl ether, menthyl propyl ether, menthyl isobutyl ether, isopulegylmethyl ether, 2-isopropylcyclohexyl methyl ether, 2-isopropylcyclohexylethyl ether, 3,3,5-trimethylcyclohexyl methyl ether,1-(3,3-dimethylcyclohexyl)-ethyl ethyl ether,1-(3,3-dimethylcyclohexyl)ethyl propyl ether, and1-(3,3-dimethylcyclohexyl)ethyl methyl ether.

[0026] The activity of causing a refreshing clearing feeling in themouth, pharyngeal cavity and the airways, in the case of the inventiverhinologically active compounds, applies to all isomeric forms, that isto say to diastereomers and enantiomers.

[0027] The following acyclic ethers for the inventive rhinologicallyactive compounds are novel:

[0028] Isopulegyl methyl ether, 1-(3,3-dimethylcyclohexyl)ethyl ethylether, 1-(3,3-dimethylcyclohexyl)ethyl propyl ether and1-(3,3-dimethyl-cyclohexyl)ethyl methyl ether.

[0029] Preparation of the acyclic ethers for the inventiverhinologically active compounds is known per se. It can be performed,for example, by etherification of the corresponding alcohols withalkylating agents, such as alkyl halides, alkyl tosylates, alkylmesylates or alkyl halides in the presence of an equivalent amount of abasic compound. Particularly advantageous here is etherification by thephase-transfer process, which is described, for example, in Angew. Chem.85, 868-869 (1973), and is carried out as follows: the alcohol to beetherified is vigorously stirred in a nonpolar solvent in the presenceof a phase-transfer catalyst, for example tetrabutylammonium iodide,with a 2.5-fold excess of 50% strength sodium hydroxide solution and1.2-fold excess of an alkylating agent is added. After a customarycleanup, the corresponding ether is obtained, which is separated offfrom unreacted alcohol by distillation or liquid chromatography.

[0030] To achieve fresh ethereal, minty, cooling, sweet and fruityflavor notes in combination with a refreshing clearing feeling in themouth, pharyngeal cavity and the airways, the inventive rhinologicallyactive compounds can be combined with one another in pure form, or, in apreferred form, can be combined with aroma substances or flavorsubstances.

[0031] Suitable aroma substances are both complex natural raw materials,such as extracts and essential oils produced from plants, and fractionsand homogeneous substances produced therefrom, and also homogeneoussynthetically or biotechnologically produced aroma substances.

[0032] Examples of natural raw materials are, for example: peppermintoils, spearmint oils, Mentha arvensis oils, aniseed oils, clove oils,citrus oils, cinnamon bark oils, winter green oils, cassia oils, davanaoils, spruce needle oils, eucalyptus oils, fennel oils, galbanum oils,ginger oils, camomile oils, cumin oils, rose oils, geranium oils, sageoils, yarrow oils, star anise oils, thyme oils, juniper berry oils,rosemary oils, angelica root oils, and fractions of these oils.

[0033] Examples of homogeneous aroma substances are, for example:anethole, menthol, menthone, isomenthone, menthyl acetate, menthofuran,mint lactone, eucalyptol, limonene, eugenol, pinene, sabinene hydrate,3-octanol, carvone, gamma-octalactone, gamma-nonalactone, germacrene-D,viridiflorol, 1,3E,5Z-undecatriene, isopulegol, piperitone, 2-butanone,ethyl formate, 3-octyl acetate, isoamyl isovalerate, hexanol, hexanal,cis-3-hexenol, linalool, alpha-terpineol, cis and trans carvyl acetate,p-cymol, damascenon, damascone, rose oxide, dimethyl sulfide, fenchol,acetaldehyde diethyl acetal, cis-4-heptenal, isobutyraldehyde,isovaleraldehyde, cis-jasmone, anisaldehyde, methyl salicylate, myrtenylacetate, 2-phenylethyl alcohol, 2-phenylethyl isobutyrate, 2-phenylethylisovalerate, cinnamaldehyde, geraniol, nerol. In the case of chiralcompounds, the aroma substances can be present as racemate or anindividual enantiomer or as enantiomer-enriched mixture.

[0034] Examples of other flavor substances which can be advantageouslycombined with the inventive rhinologically active substances are, forexample, substances having a physiologically cooling action, that is tosay substances which cause an impression of cold in the mucousmembranes. Such substances having a cooling action are, for example,l-menthol, 1-isopulegol, menthone glycerol acetal, menthyl lactate,substituted menthane-3-carboxamides (for exampleN-ethylmenthane-3-carboxamide), 2-isopropyl-N,2,3-trimethylbutanamide,substituted cyclohexanecarboxamides, 3-menthoxy-1,2-propanediol,2-hydroxyethylmenthyl carbonate, 2-hydroxypropylmenthyl carbonate,N-acetylglycine menthyl ester, menthylhydroxycarboxylic esters (forexample menthyl 3-hydroxybutyrate), menthyl monosuccinate,2-mercaptocyclodecanone, and menthyl 2-pyrrolidin-5-one carboxylate.

[0035] The inventive rhinologically active substances can be present inthe aroma or flavor substance compositions at a content of 0.1 to 100%by weight. Preference is given to a content of 0.1 to 70% by weight;more preference is given to a content of 0.5 to 40% by weight.

[0036] The aroma or flavor substance compositions comprising theinventive rhinologically active substances can be used in pure form, assolutions, or else in specially prepared form, and incorporated intoready-to-use products.

[0037] Suitable solvents are, for example, ethyl alcohol, 1,2-propyleneglycol, triacetin, benzyl alcohol and fatty oils, for example coconutoil or sunflower seed oil.

[0038] The aroma or flavor substance compositions comprising theinventive rhinologically active substances can also comprise additivesand aids, for example preservatives, pigments, antioxidants, anticakingagents, thickeners, etc.

[0039] In particular prepared forms, the aroma or flavor substancecompositions comprising the inventive rhinologically active substancescan be bound to a carrier, spray-dried or else encapsulated.

[0040] In the bound form, the aroma or flavor substance compositions canbe bound on or in a carrier, for example sodium chloride, sugar,starches or sugar melts.

[0041] The spray-dried form is produced from the liquid compositions byproducing an emulsion with addition of defined amounts of a carrier,preferably biopolymers such as starch, modified starches, maltodextrinand gum arabic. This emulsion is dried in spray-dryers by very finedistribution with uniform temperature application. A powder resultshaving the desired loading of liquid composition.

[0042] The encapsulated form is also produced from the liquidcompositions by adding a carrier. Various technologies exist by whichcapsules can be produced. The most familiar are extrusion,spray-granulation and coacervation. The particle sizes customarilyextend from 10 μm to 5 mm. The most familiar capsule materials arevarious starches, maltodextrin and gelatin. In these capsules, theliquid or solid aroma or flavor substance compositions are enclosed andcan be released by various mechanisms such as use of heat, pH shift orchewing pressure.

[0043] The inventive rhinologically active substances are suitable forproducing preparations of the most varied flavors, particularly for usein aroma compositions having a cooling-refreshing mint-like flavor. Themint compositions are essentially characterized by a content ofpeppermint oils, Mentha arvensis oils, spearmint oils, eucalyptus oils,1,8-cineole (eucalyptol), menthol and substances having aphysiologically cooling activity.

[0044] The contents of the individual composition constituents of themint compositions can vary here generally between 0.1 and 99.9%

[0045] Mint compositions which are preferably used are those having 1 to90% by weight of menthol, 1 to 60% by weight of menthone, 1 to 90% byweight of peppermint or Mentha arvensis oils, 1 to 90% by weight ofspearmint oils, 1 to 90% by weight of eucalyptol oreucalyptol-containing eucalyptus oils, 0.5 to 70% by weight of theinventive rhinologically active substances, for example menthyl methylether, isopulegyl methyl ether or the like and 0.5 to 70% by weight ofsubstances having a physiologically cooling action.

[0046] Mint compositions which are preferably used are those having 20to 60% by weight of menthol, 5 to 30% of menthone, 5 to 60% by weight ofpeppermint or Mentha arvensis oils, 5 to 60% by weight of spearmintoils, 2 to 50% by weight of eucalyptol or eucalyptol-containingeucalyptus oils, 0.5 to 40% by weight of the inventive rhinologicallyactive substances, for example menthyl methyl ether, isopulegyl methylether or the like and 1 to 30% by weight of substances having aphysiological cooling action.

[0047] Substances having a physiological cooling action can be theabove-described, in which case they are used individually or asmixtures. If mixtures are used, these are generally mixtures, forexample, of menthone glycerol acetal, menthyl lactate, substitutedmenthyl-3-carboxamides (for example N-ethylmenthyl-3-carboxamide),2-hydroxyethylmenthyl carbonate and 2′-hydroxypropylmenthyl carbonate.

[0048] Generally, mixtures are used which have 1 to 99% by weight ofmenthone glycerol acetal, 1 to 99% by weight of menthyl lactate, 1 to99% by weight of N-ethylmenthyl-3-carboxamide, 1 to 99% by weight of2-hydroxyethylmenthyl carbonate and 1 to 99% by weight ofhydroxypropylmenthyl carbonate.

[0049] Preference is given to mixtures having 1 to 70% by weight ofmenthone glycerol acetal, 1 to 70% by weight of menthyl lactate, 1 to70% by weight of N-ethylmenthyl-3-carboxamide, 1 to 70% by weight of2-hydroxyethylmenthyl carbonate and 1 to 70% by weight of2-hydroxypropylmenthyl carbonate.

[0050] By adding other aroma substances, for example of the sweet,sweet-aromatic, fresh, fruity types, or if appropriate, of other flavorsalso, these mint compositions can be modified in flavor, with thecontent by weight of the added aroma substances generally being 0.001 to50% by weight, based on the weight fraction of minty compounds andcooling compounds. Preference is given to an addition of 0.01 to 30% byweight, preferably an addition of 0.1 to 10% by weight, based on theweight fraction of the minty and cooling substances.

[0051] By using the inventive rhinologically active substances in suchcompositions, the content of the eucalyptus oils and of 1,8-cineole(eucalyptol) and thus the strong medicinal flavor note can be reduced,without reducing the refreshing clearing feeling in the mouth,pharyngeal cavity and the airways. The perception of freshness which isproduced by the inventive rhinologically active substances in theairways, in the mouth and in the pharyngeal cavity is of longer durationthan that caused by 1,8-cineole (eucalyptol).

[0052] It is noteworthy, here, that the flavor intensity and roundnessof flavor of the mint compositions are increased by using the inventiverhinologically active substances, and the cooling action of thesubstances having a physiological cooling action is intensified.

[0053] The preparations comprising the inventive rhinologically activesubstances can advantageously be used, especially in oral carecompositions, such as toothpastes and mouthwashes, chewing-gum, foods,such as confectionery and sweets for sucking, luxury consumptionmerchandise, such as tobacco, pharmaceutical preparations, nasal sprays.

[0054] The content of the preparations comprising the inventiverhinologically active substances is, in ready-to-use mouthwashes 0.01 to1% by weight, preferably 0.1 to 0.3% by weight. In mouthwashconcentrates, the content of the compositions comprising the inventiverhinologically active substances is between 0.01 and 20% by weight,preferably 0.1 to 10% by weight, and more preferably 3 to 5% by weight.In toothpastes and chewing-gum, the compositions comprising theinventive rhinologically active substances are used at a concentrationbetween 0.1 and 5% by weight, preferably 0.5 to 2% by weight, and morepreferably between 0.8 and 1.5% by weight. In sweets for sucking, thecontent of the compositions comprising the inventive rhinologicallyactive substances is between 0.01 and 2% by weight, preferably 0.05 to 1% by weight; and more preferably between 0.1 and 0.5%.

[0055] Toothpastes that are flavored with the compositions comprisingthe inventive rhinologically active substances generally consist of anabrasive system (abrasives or polishes), for example silicic acids,calcium carbonates, calcium phosphates, aluminum oxides and/or hydroxylapatites; surface-active substances, for example sodium lauryl sulphate,sodium lauryl sarcosinate and/or cocamidopropylbetaine; humectants, forexample glycerol and/or sorbitol; thickeners, for example carboxymethylcellulose, polyethylene glycols, carrageenans and/or Laponites®,sweeteners, for example saccharin; stabilizers; and active compounds,for example sodium fluoride, sodium monofluorophosphate, tin difluoride,quaternary ammonium fluorides, zinc citrate, zinc sulphate, tinpyrophosphate, tin dichloride, mixtures of various pyrophosphates,triclosan, cetylpyridinium chloride, aluminum lactate, potassiumcitrate, potassium nitrate, potassium chloride, strontium chloride,hydrogen peroxide and/or sodium bicarbonate.

[0056] Chewing-gum that is flavored with the compositions comprising theinventive rhinologically active substances generally consists of achewing-gum base, that is to say a chewing mass which becomes plastic onchewing; sugars of various types; sugar substitutes; sweeteners; sugaralcohols; humectants; thickeners; emulsifiers; and stabilizers.

[0057] When finished products that comprise the compositions having theinventive rhinologically active substances are used, it is found thatthe inventive rhinologically active substances or the compositionscomprising the inventive rhinologically active substances areparticularly suitable for freshening the breath and neutralizing orreducing bad breath.

[0058] The use of the inventive rhinologically active substances or thecompositions comprising the rhinologically active substances in oralcare products, for example mouthwashes and toothpastes, and chewing-gum,leads to unpleasant, especially bitter, taste impressions being maskedor neutralized, as are caused, for example, by substances such astriclosan, zinc citrate, zinc sulphate, polyphosphates andpyrophosphates, bicarbonates, strontium salts and potassium salts, tinpyrophosphate, tin chloride, aluminum lactate, hydrogen peroxide,fluorides, vitamins, cetylpyridinium chloride, and emulsifiers, forexample, particularly sodium lauryl sulphate, sodium lauryl sarcosinateand cocamidopropylbetaine, and sweeteners, for example aspartame,saccharin, acesulfame-K, sorbitol; xylitol, cyclamates (for examplesodium cyclamate), sucralose, alitame, neotame, thaumatin, neohesperidinDC, maltitol, lactitol or chewing-gum bases.

[0059] A further positive property of the inventive rhinologicallyactive substances which must be emphasized is their stability intoothpastes based on chalk or bicarbonate which, because of theiralkaline pH, are difficult to flavor.

[0060] The inventive rhinologically active substances and thecompositions comprising the inventive rhinologically active substancesare also suitable, however, for use in pharmaceutical preparations, forexample, nasal drops and nasal sprays or embrocations. The compositionscomprising the inventive rhinologically active substances are suitable,in particular, for masking the bitter taste of medicaments.

EXAMPLES

[0061] The examples below are intended to illustrate the use of theinventive rhinologically active substances. However, the use of theinventive rhinologically active substances is not restricted to theexamples cited.

Example 1

[0062] Preparation of the Alkyl Ethers

[0063] General Instructions:

[0064] 1 mol of the alcohol to be etherified is dissolved in 400 ml oftoluene and stirred vigorously after addition of 2.6 mol. of 50%strength sodium hydroxide solution and 2 g of tetrabutylammonium iodide.At a bottom temperature of a maximum of 45° C., 1.2 mol of alkylatingagent is added in the course of 1 h. The mixture is then stirred for afurther 3 h at this temperature. If dialkyl sulphates were used as analkylating agent, ammonia is added to destroy them and the mixture isstirred for a further 30 min at room temperature. After addition ofwater, the phases are separated. The solvent is taken off from theorganic phase and the residue is fractionated by distillation. The pureethers are obtained by redistillation via a split-tube column.

[0065] In this manner the following ethers were prepared: TABLE 1Compound: Mass spectrum: Menthyl methyl ether m/z = 170 155 138 123 9585 81 67 55 45 41 % 1 2 45 19 36 100 49 18 27 15 28 Menthyl ethyl etherm/z = 184 138 123 113 99 95 81 71 55 41 % 2 36 12 8 100 20 26 28 18 20Menthyl propyl ether m/z 198 138 123 113 95 81 71 55 41 % 2 46 16 100 2633 63 22 29 Menthyl isobutyl ether m/z 212 138 127 123 95 83 81 71 57 5541 % 2 43 76 21 34 38 53 100 43 28 34 2-Isopropylcyclohexyl methyl etherm/z 156 141 124 113 109 99 95 81 71 67 55 41 % 5 12 100 16 58 21 23 6090 36 25 56 2-Isopropylcyclohexyl ethyl ether m/z 170 155 127 124 109 9995 85 81 67 57 41 % 8 16 24 100 55 18 20 96 50 26 75 381-(3,3-Dimethylcyclohexyl)ethyl ethyl ether m/z 184 123 81 73 69 55 4541 28 % 2 16 8 100 7 10 59 14 10 1-(3,3-Dimethylcyclohexyl)ethyl propylether m/z 198 183 123 87 81 69 55 45 41 % 1 2 16 93 9 14 13 100 231-(3,3-Dimethylcyclohexyl)ethyl methyl ether m/z 170 155 123 110 95 8169 59 55 41 % 1 3 13 5 6 9 7 100 10 12 3,3,5-Trimethylcyclohexyl methylether m/z 156 141 124 109 99 85 67 58 55 41 % 4 3 29 61 87 100 23 18 2830 Isopulegyl methyl ether m/z 168 153 136 121 111 98 93 85 81 67 55 41% 18 13 9 41 30 34 28 100 24 21 23 25

Example 2

[0066] Production of a toothpaste flavoring of the eucalyptus mentholtype, using menthyl methyl ether: The following were mixed: 0.5 parts byweight camphor 3 parts by weight anethole 6 parts by weight peppermintoil of the Mentha arvensis type 2 parts by weight menthyl lactate 2parts by weight 2-hydroxyethylmenthyl carbonate 2 parts by weight2-hydroxypropylmenthyl carbonate 20 parts by weight 1,8-cineole(eucalyptol) 64.5 parts by weight I-menthol

[0067] In a second mixture batch, the 1,8-cineole (eucalyptol) contentwas replaced by l-menthyl methyl ether. Both flavorings are incorporatedat a concentration of 1.3% by weight into a standard toothpaste mixbased on silicic acid. Both types of toothpaste were tested underconditions of practice by an expert panel trained in sensory testing.The result showed that the flavoring containing l-menthyl methyl etherand without 1,8-cineole (eucalyptol) markedly decreased the stronglymedicinal taste, without the taste impression of freshness in theairways, mouth and pharyngeal cavity being reduced. Overall, the secondflavoring led to a more clear longer-lasting taste impression with moreroundness and volume.

[0068] Comparable effects are obtained if isopulegyl methyl ether,3,3,5-trimethylcyclohexyl methyl ether or 1-(3,3-dimethylcyclohexyl)ethyl methyl ether were used instead of l-menthyl methyl ether.

Example 3

[0069] Production of toothpaste flavoring of the wintergreen type usingmenthyl methyl ether: The following were mixed: 10 parts by weightanethol 5 parts by weight peppermint oil of the Mentha arvensis type 5parts by weight peppermint oil of the Mentha piperita type 25 parts byweight methyl salicylate 40 parts by weight I-menthol 15 parts by weightI-menthyl methyl ether

[0070] The flavoring was incorporated at a concentration of 1.3% byweight into a standard toothpaste mix based on silicic acid. Thetoothpaste was tested under conditions of practice by an expert paneltrained in sensory testing. The results showed that the flavoring gave ataste impression of high intensity and long-lasting duration, apronounced markedly refreshing, clearing feeling being perceived in theairways, in the mouth and in the pharyngeal cavity.

Example 4

[0071] Production of a chewing-gum flavoring using l-menthyl methylether: The following were mixed: 40 parts by weight peppermint oil ofthe Mentha arvensis type 20 parts by weight I-menthone 20 parts byweight I-menthol 20 parts by weight I-menthyl methyl ether

[0072] The flavoring was incorporated at a concentration of 1.5% byweight into a sugar-free standard chewing-gum base. The chewing gum wastested for a sensory quality by a trained expert panel. It was foundthat addition of l-menthyl methyl ether gave a markedly refreshingclearing feeling in the airways, in the mouth and in the pharyngealcavity, and the taste roundness and intensity of the peppermintflavoring was markedly increased.

[0073] Although the invention has been described in detail in theforegoing for the purpose of illustration, it is to be understood thatsuch detail is solely for that purpose and that variations can be madetherein by those skilled in the art without departing from the spiritand scope of the invention except as it may be limited by the claims.

What is claimed is:
 1. Rhinologically active substances of the formula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 2. Rhinologically activesubstances according to claim 1, wherein R¹ denotes a methyl or ethylgroup, and R³ denotes a monocyclic carbon system having 6 or 7 carbonatoms that can be unsubstituted or substituted with further alkyl groupshaving 1 to 3 carbon atoms and/or alkenyl groups having 3 carbon atoms.3. Rhinologically active substances according to claim 1, wherein saidrhinologically active substances are selected from the group consistingof l-menthyl methyl ether, d-menthyl methyl ether, dl-menthyl methylether, menthyl ethyl ether, menthyl propyl ether, menthyl isobutylether, isopulegyl methyl ether, 2-isopropylcyclohexyl methyl ether,2-isopropylcyclohexyl ethyl ether, 3,3,5-trimethylcyclohexyl methylether, 1-(3,3-dimethylcyclohexyl)ethyl ethyl ether,1-(3,3-dimethylcyclohexyl)ethyl propyl ether, and1-(3,3-dimethylcyclohexyl)ethyl methyl ether.
 4. Preparations having arefreshing activity comprising rhinologically active substances of theformula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 5. Preparations having arefreshing activity according to claim 4, wherein R¹ denotes a methyl orethyl group, and R³ denotes a monocyclic carbon system having 6 or 7carbon atoms that can be unsubstituted or substituted with further alkylgroups having 1 to 3 carbon atoms and/or alkenyl groups having 3 carbonatoms.
 6. Preparations having a refreshing activity according to claim4, comprising rhinologically active substances selected from the groupconsisting of l-menthyl methyl ether, d-menthyl methyl ether, dl-menthylmethyl ether, menthyl ethyl ether, menthyl propyl ether, menthylisobutyl ether, isopulegyl methyl ether, 2-isopropylcyclohexyl methylether, 2-isopropylcyclohexyl ethyl ether, 3,3,5-trimethylcyclohexylmethyl ether, 1-(3,3-dimethylcyclohexyl)ethyl ethyl ether,1-(3,3-dimethylcyclohexyl)ethyl propyl ether, and1-(3,3-dimethylcyclohexyl)ethyl methyl ether.
 7. Preparations having arefreshing activity according to claim 4, wherein said preparationscomprise 0.0001 to 10% by weight of said rhinologically activesubstances.
 8. An oral care composition comprising preparations having arefreshing activity comprising rhinologically active substances of theformula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 9. An oral care compositionaccording to claim 8, wherein said oral care composition is atoothpaste.
 10. An oral care composition according to claim 8, whereinsaid oral care composition is a mouthwash.
 11. An oral care compositionaccording to claim 8, wherein said oral care composition is achewing-gum.
 12. A food product comprising preparations having arefreshing activity comprising rhinologically active substances of theformula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 13. Tobacco productscomprising preparations having a refreshing activity comprisingrhinologically active substances of the formula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 14. Confectionary productscomprising preparations having a refreshing activity comprisingrhinologically active substances of the formula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 15. Pharmaceuticalpreparations having a refreshing activity comprising rhinologicallyactive substances of the formula

wherein x is 0 or 1, R¹ denotes an alkyl group having 1 to 4 carbonatoms, R² denotes a methyl or ethyl group and R³ denotes a monocycliccarbon system having 5, 6, 7 or 8 carbon atoms that can be unsubstitutedor substituted with further alkyl groups having 1 to 4 carbon atoms oralkenyl groups having 2 to 4 carbon atoms.
 16. Novel acyclic ethersselected from the group consisting of isopulegyl methyl ether,1-(3,3-dimethylcyclohexyl)ethyl ethyl ether,1-(3,3-dimethylcyclohexyl)ethyl propyl ether and1-(3,3-dimethylcyclohexyl)ethyl methyl ether.